Elsevier

Tetrahedron

Volume 67, Issue 20, 20 May 2011, Pages 3705-3713
Tetrahedron

Covalent nano-clip and nano-box compounds based on free base porphyrins

https://doi.org/10.1016/j.tet.2011.03.072Get rights and content

Abstract

Novel nano-clip and nano-box compounds were obtained by reaction between dibromomethane and 5,15-di[p-(9-methoxytriethylenenoxy)phenyl]-10,20-di[p-hydroxyphenyl]porphyrin. The molecular architecture varies from a co-facial (nano-clip) to a four wall-box (nano-box) structure. The products were characterized by 1H NMR and UV–vis spectroscopy and MALDI-TOF mass spectrometric analysis.

The UV–vis spectra of the nano-clip showed a modification of the characteristic porphyrin soret and Q bands, with respect to the monomer and cyclic tetramer, as a probable consequence of a hybrid orbital deformation (HOD) phenomenon involving the two porphyrin π rings forced to a closer co-facial spatial arrangement. The spatial distance between the two co-facial porphyrin units, and therefore the molecular cavity size, can be modified inducing an electrostatic repulsion by means of a reversible protonation of the pyrrolic cores. The 1H NMR spectra of the nano-box showed a strong high-field shift of some aromatic and ether protons present in the upper and lower rim of the molecular box.

Introduction

There is an increasing interest in developing smart nano-structures for applications in many different fields, from environmental monitoring to biological, medical and industrial chemistry. For some specific properties (e.g., strong molar absorption, bound metal atoms in pyrrolic cores, extensive aromatic structures, peculiar affinity for neoplastic cells, etc.), porphyrin derivatives are among the most studied compounds, and some applications like chemical and/or biological receptors, artificial sensors for drug determinations, mimesis of biological systems, etc., are already well-defined.1, 2, 3, 4, 5, 6, 7, 8, 9, 10 Furthermore, because of their tendency to accumulate in cancer cells, some of these synthetic structures have already been tested for drug-delivery in cancerous diseases.

In the presence of the appropriate molecules and/or external stimuli, these systems can change their physicochemical properties in a characteristic and measurable manner (as a consequence of structural modification due to supramolecular complex formation or to chemical alteration) performing, in some cases, a specific task. For instance, some linearly conjugated poly-porphyrins behave like photon nano-wires,11 whereas cyclic porphyrins, coupled with electron acceptor units (i.e., fullerenes), are used as light-harvesting systems.12 In addition, some porphyrin structures are used as enzyme mimics,13 etc.

More recently, several 3D cyclic oligo-porphyrins with different architectures [e.g., spheres, prisms, regular polyhedra (with a varying number of faces), etc.] have been studied.14, 15, 16, 17 The properties of these molecules may depend on the size and hydrophobic nature of the cavities inside their 3D structure18 (for example, suitable to accommodate hydrophobic chemicals) as well as the presence of functional groups.

We recently reported some work regarding the synthesis of some uncharged water-soluble porphyrins19 and bis-porphyrins,20 and the modification of their spectroscopic properties (i.e., NMR, UV–vis and circular dichroism) when treated with aliphatic and aromatic α-l-amino acids.

In particular, it was found that their qualitative bio-molecular recognition properties depend strongly on the porphyrin structure. Mono-porphyrins were tools for the recognition of enantiomeric species and discrimination between aliphatic and aromatic aminoacids,21, 22 while bis-porphyrins, arranged as molecular tweezers, were useful for the recognition of bio-molecules having different sizes.23

In the present paper, as the first step in the preparation of water-soluble nano-clip and nano-box compounds, the synthesis and characterization of some novel cyclic ethers, constituted by two (nano-clip) or four (nano-box) porphyrin units and spaced with methylene bridges, are reported. These compounds, obtained by the reaction between dibromomethane and 5,15-di[p-(9-methoxytriethylenenoxy)phenyl]-10,20-di[p-hydroxyphenyl]porphyrin, have a co-facial (nano-clip) or a four wall-box (nano-box) architecture. Planar isomeric cyclic porphyrin ethers, starting from the 5,10-di[p-(9-methoxytriethylenenoxy)phenyl]-15,20-di[p-hydroxyphenyl]porphyrin, were also prepared to verify the dependence of the spectroscopic data on the molecular arrangement.

The aim of these syntheses was to obtain molecular systems for the recognition and/or the carriage of bio-molecules. Spectroscopic data of the nano-clip showed modified soret and Q-bands, with respect to the monomer and cyclic tetramer. An UV–vis titration allowed verification of the easy and reversible protonation of the pyrrolic cores which, by electrostatic repulsion, modifies the spatial distance between the two co-facial porphyrins and, therefore, the cavity size. This reversible modification could be used to change the dimer molecule status from open to closed, and facilitate the accommodation or release of suitable chemical species, acting then as a drug carrier.

The tetrameric porphyrin molecule (nano-box) could also be used as a drug carrier, forming an inclusion complex with macromolecular drugs, or as a nano-reactor, for the peculiar nano-space conditions inside the box. In this case, 1H NMR spectroscopic analysis showed a high-field shift of the aromatic and ether protons present in the upper and lower box rims as a specific characteristic of this molecular structure.

These compounds differ from previous analogous porphyrinic systems14, 15, 16, 17 in that their totally covalent structure makes them more versatile potential macromolecular tools.

Section snippets

Results and discussion

The synthesis of cyclic oligomers containing porphyrin units involved the use of 5,15-di[p-(9-methoxytriethyleneoxy)phenyl]-10,20-di[p-hydroxyphenyl]porphyrin [indicated as HO(H2–PTTEG2)OH] or 5,10-di[p-(9-methoxytriethyleneoxy)phenyl]-15,20-di[p-hydroxyphenyl]porphyrin [indicated as HO(H2–PCTEG2)OH] in turn obtained by the reaction between tetrakis-p-(hydroxyphenyl)porphyrin and 9-methyltriethyleneoxy chloride (see Experimental section).

Pure HO(H2–PTTEG2)OH and HO(H2–PCTEG2)OH were collected

Conclusion

In summary we report the synthesis and NMR, UV–vis and MALDI-TOF characterization of novel cyclic oligomers containing two or four porphyrin units. In particular, in the case of cy-[O–(H2–PTTEG2)–O–CH2–]2 cyclic dimer, the observed UV–vis red-shift of soret and Q-bands was attributed to the hybrid orbital deformation (HOD) phenomenon or to electronic interactions between the two porphyrin rings, forced into a co-facial structure. It was also ascertained that upon acid treatment, the inter-space

General

The structures of the cyclic nano-clips and nano-box porphyrin compounds were characterized by 1H NMR analyses. 1H NMR, COSY and T-ROESY spectra were obtained on an UNITYINOVA Varian instrument operating at 500 MHz (1H) using VNMR for software acquisition and processing. Samples were dissolved in CDCl2CDCl2 and the chemical shifts were expressed in parts per million compared to the CHCl2CHCl2 residue signal. The spectra were acquired at 323 K, with a spin lock time of 0.5 s. COSY and T-ROESY

Acknowledgements

The authors thank the Ministero Istruzione Università e Ricerca (MIUR, Roma) for the partial financial support (PRIN 2008—‘New Porphyrins as Chirogenetic Probes to Recognition of Peptides and Proteins of Biological Interest’—N. Prot. 2008KHW8K4) and the National Research Council (CNR, Roma). Thanks are due to Mr. R. Rapisardi for his contribution to the MALDI-TOF measurements.

References and notes (29)

  • M.A. Awawdeh et al.

    Sens. Actuators, B

    (2003)
  • C. Verchere-Beaur et al.

    J. Inorg. Biochem.

    (1990)
  • M. Balaz et al.

    Angew. Chem.

    (2005)
  • P.P. Pompa et al.

    Phys. Rev. E

    (2004)
  • C. Czeslik et al.

    Phys. Rev. E

    (2004)
  • A. D’Urso et al.

    J. Am. Chem. Soc.

    (2009)
  • Y. Aoyama et al.

    J. Am. Chem. Soc.

    (1988)
  • T. Mizutani et al.

    J. Am. Chem. Soc.

    (1999)
  • E. Mikros et al.

    Inorg. Chem.

    (1991)
  • V.V. Borovkov et al.

    J. Am. Chem. Soc.

    (2001)
  • Y.H. Kim et al.

    J. Am. Chem. Soc.

    (2001)
  • A. Ambroise et al.

    Org. Lett.

    (2000)
    I. Hwang et al.

    J. Am. Chem. Soc.

    (2004)
  • H.L. Anderson et al.

    J. Chem. Soc., Perkin Trans. 1

    (1995)
  • H.L. Anderson et al.

    J. Chem. Soc., Perkin Trans. 1

    (1995)
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